한국임상약학회지 (Korean Journal of Clinical Pharmacy)

  • 제22권1호
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  • Pages.21-29
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  • 2012
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  • 1226-6051(pISSN)
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  • 2508-786X(eISSN)
한국임상약학회 (Korean College Of Clinical Pharmacy)
권호 표지

생명공학의약품의 약동학 시험 지침 개발 연구

Development of Guidance on the Pharmacokinetic Studies of Therapeutic Biologics

  • 이혜원 (경북대학교 일반대학원 의과학과 및 경북대학교병원 임상시험센터) ;
  • 임미선 (경북대학교 일반대학원 의과학과 및 경북대학교병원 임상시험센터) ;
  • 성숙진 (경북대학교 일반대학원 의과학과 및 경북대학교병원 임상시험센터) ;
  • 이주미 (경북대학교 일반대학원 의과학과 및 경북대학교병원 임상시험센터) ;
  • 박성민 (경북대학교 일반대학원 의과학과 및 경북대학교병원 임상시험센터) ;
  • 노금한 (영남대학교 약학대학) ;
  • 박성호 (영남대학교 약학대학) ;
  • 김은정 (식품의약품안전청 약리연구과) ;
  • 강원구 (영남대학교 약학대학) ;
  • 윤영란 (경북대학교 일반대학원 의과학과 및 경북대학교병원 임상시험센터)
  • Lee, Hae-Won (Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital) ;
  • Lim, Mi-Sun (Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital) ;
  • Seong, Sook-Jin (Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital) ;
  • Lee, Joo-Mi (Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital) ;
  • Park, Sung-Min (Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital) ;
  • Noh, Keum-Han (College of Pharmacy, Yeungnam University) ;
  • Park, Sung-Ho (College of Pharmacy, Yeungnam University) ;
  • Kim, Eun-Jung (Pharmacological Research Division, Korea Food & Drug Administration) ;
  • Kang, Won-Ku (College of Pharmacy, Yeungnam University) ;
  • Yoon, Young-Ran (Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital)
  • 투고 : 2011.11.18
  • 심사 : 2012.01.17
  • 발행 : 2012.03.31
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초록

Modern biologics are biotechnology-derived therapeutics, including recombinant therapeutic proteins like monoclonal antibodies, cytokines and tissue growth factors. Although the pharmacokinetics of therapeutic biologics should be evaluated based on the same general principles as small molecules, careful considerations should be given to bioanalytics and pharmacokinetics when designing pharmacokinetic studies of biologics during their drug development, due to their different physicochemical properties compared with small molecules. The aim of this study was to develop a draft guidance on pharmacokinetic studies of therapeutic biologics in clinical studies. All the elements outlined in the current Food and Drug Administration (FDA), European Medicinal Agency (EMEA), and International Conference on Harmonisation (ICH) guidelines and regulations, and the related literatures previously published were searched and evaluated. In this draft guidance, the specific problems related to the pharmacokinetics of therapeutic biologics that need special consideration during drug development process were addressed, and differences in pharmacokinetic characteristics between biologics and small molecules affecting the content of the development programme were presented.

키워드

참고문헌

  1. Baumann A. Early development of therapeutic biologics - pharmacokinetics. Curr Drug Metab 2006; 7(1): 15-21. https://doi.org/10.2174/138920006774832604
  2. Tang L, Persky AM, Hochhaus G, et al., Pharmacokinetic aspects of biotechnology products. J Pharm Sci 2004; 93(9): 2184-204. https://doi.org/10.1002/jps.20125
  3. Guideline on the Clinical Investigation of the Pharmacokinetics of Therapeutic Proteins (EMEA/CHMP/ EWP/89249/2004, adopted in January 2007).
  4. Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Non-clinical and Clinical Issues (EMEA/ CHMP/BMWP/42832/2005, adopted in February 2006).
  5. Guideline on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients with Impaired Hepatic Function (EMEA/CPMP/EWP/2339/02, adopted in February 2005).
  6. Note for Guidance on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients with Impaired Renal Function (EMEA/CHMP/EWP/225/02, adopted in June 2004).
  7. Note for Guidance on the Investigation of Drug Interactions (EMEA/CPMP/EWP/560/95, adopted in December 1997).
  8. Note for Guidance on the Investigation of Bioavailability and Bioequivalence (EMEA/CPMP/EWP/QWP/1401/98, adopted in July 2001).
  9. 생물의약품 비임상시험 가이드라인 2008년 12월 식품의약품안전청 생물의약품국 세균백신과
  10. 임상시험용 생물학적제제등 품질평가 가이드라인(안) 2008년 12월 식약청 생물의약품국
  11. 동등생물의약품 평가 가이드라인 (Guidelines on the Evaluation of Biosimilar Products) 2010년 12월 식품의약품 안전청 바이오생약심사부 첨단제제과
  12. ICH S6: Preclinical Safety Evaluation of Biotechnology- Derived Pharmaceuticals (CPMP/ICH/302/95, adopted in September 1997).
  13. ICH E3: Structure and Content of Clinical Study Report (CPMP/ICH/137/95, adopted in December 1995).
  14. ICH E6: Guideline for Good Clnical Practice (CPMP/ICH/ 135/95/Step4, adopted in June 1996).
  15. ICH E8: General Considerations for Clinical Trials (CPMP/ICH/291/95, adopted in September 1997).
  16. ICH Q2: Validation of Analytical Procedures: Text and Methodology (CPMP/ICH/281/95, adopted in December 1996).
  17. Pechstein B, Nagaraja NV, Hermann R, et al., Pharmacokinetic-pharmacodynamic modeling of testosterone and luteinizing hormone suppression by cetrorelix in healthy volunteers. J Clin Pharmacol 2000; 40: 266-74. https://doi.org/10.1177/00912700022008937
  18. Miyatake A, Morimoto Y, Oishi T, et al., Circadian rhythm of serum testosterone and its relation to sleep: comparison with the variation in serum luteinizing hormone, prolactin, and cortisol in normal men. J Clin Endocrinol Metab 1980; 51(6): 1365-71. https://doi.org/10.1210/jcem-51-6-1365
  19. Mullis PE, Pal BR, Matthews DR, et al., Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus. Clin Endocrinol 1992; 36(3): 255-63. https://doi.org/10.1111/j.1365-2265.1992.tb01441.x
  20. Mahmood I. Methods to determine pharmacokinetic profiles of therapeutic proteins. Drug Discov Today Technol 2008; 5(2-3): e65-9. https://doi.org/10.1016/j.ddtec.2008.12.001
  21. Beshyah SA, Anyaoku V, Niththyananthan R, et al., The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh. Clin Endocrinol 1991; 35(5): 409-12. https://doi.org/10.1111/j.1365-2265.1991.tb03557.x
  22. Marshall SA, Lazar GA, Chirino AJ, et al., Rational design and engineering of therapeutic proteins. Drug Discov Today 2003; 8(5): 212-21. https://doi.org/10.1016/S1359-6446(03)02610-2
  23. Galluppi GR, Rogge MC, Roskos LK, et al., Integraion of pharmacokinetic and pharmacodynamic studies in the discovery, development, and review of protein therapeutic agents: A conference report. Clin Pharmacol Ther 2001; 69: 387-99. https://doi.org/10.1067/mcp.2001.115455
  24. 안병진, 임동석. 생물공학제제의 약동학과 약력학. 임상약리학회지 2008; 16(2): 67-76.
  25. Schellekens H. Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther 2002; 24(11): 1720-40. https://doi.org/10.1016/S0149-2918(02)80075-3
  26. Crommelin DJA, Storm G, Verrijk R, et al., Shifting paradigms: biopharmaceuticals versus low molecular weight drugs. Int J Pharmaceut 2003; 266: 3-16. https://doi.org/10.1016/S0378-5173(03)00376-4
  27. Kessler M, Goldsmith D, Schellekens H. Immunogenicity of biopharmaceuticals. Nephrol Dial Transplant 2006; 21[Suppl5]: v9-12. https://doi.org/10.1093/ndt/gfl476
  28. Lofgren JA, Wala I, Koren E, et al., Detection of neutralizing anti-therapeutic protein antibodies in serum or plasma samples containing high levels of the therapeutic protein. J Immunol Methods 2006; 308: 101-8. https://doi.org/10.1016/j.jim.2005.10.007